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基于系统的犬新孢子虫基因组分析确定了有助于异宿主生命周期的途径。

Systems-based analysis of the Sarcocystis neurona genome identifies pathways that contribute to a heteroxenous life cycle.

作者信息

Blazejewski Tomasz, Nursimulu Nirvana, Pszenny Viviana, Dangoudoubiyam Sriveny, Namasivayam Sivaranjani, Chiasson Melissa A, Chessman Kyle, Tonkin Michelle, Swapna Lakshmipuram S, Hung Stacy S, Bridgers Joshua, Ricklefs Stacy M, Boulanger Martin J, Dubey Jitender P, Porcella Stephen F, Kissinger Jessica C, Howe Daniel K, Grigg Michael E, Parkinson John

机构信息

Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.

Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

mBio. 2015 Feb 10;6(1):e02445-14. doi: 10.1128/mBio.02445-14.

DOI:10.1128/mBio.02445-14
PMID:25670772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4337577/
Abstract

UNLABELLED

Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.

IMPORTANCE

Sarcocystis neurona is a member of the coccidia, a clade of single-celled apicomplexan parasites responsible for major economic and health care burdens worldwide. A cousin of Plasmodium, Cryptosporidium, Theileria, and Eimeria, Sarcocystis is one of the most successful parasite genera; it is capable of infecting all vertebrates (fish, reptiles, birds, and mammals-including humans). The past decade has witnessed an increasing number of human outbreaks of clinical significance associated with acute sarcocystosis. Among Sarcocystis species, S. neurona has a wide host range and causes fatal encephalitis in horses, marine mammals, and several other mammals. To provide insights into the transition from a purely enteric parasite (e.g., Eimeria) to one that forms tissue cysts (Toxoplasma), we present the first genome sequence of S. neurona. Comparisons with other coccidian genomes highlight the molecular innovations that drive its distinct life cycle strategies.

摘要

未标注

肉孢子虫属神经元种(Sarcocystis neurona)是球虫纲的成员,球虫纲是一类单细胞寄生虫,在医学和兽医学上具有重要意义,包括艾美耳属(Eimeria)、肉孢子虫属、新孢子虫属(Neospora)和弓形虫属(Toxoplasma)。与单宿主肠道病原体艾美耳属不同,肉孢子虫属、新孢子虫属和弓形虫属是双宿主寄生虫,可在多种中间宿主中感染并产生具有感染性的组织包囊。作为一个属,肉孢子虫属是最成功的原生动物寄生虫之一;所有脊椎动物,包括鸟类、爬行动物、鱼类和哺乳动物,都是至少一种肉孢子虫属物种的宿主。在此,我们对致死性马属动物原虫性脑脊髓炎的病原体肉孢子虫属神经元种进行了测序。肉孢子虫属神经元种的基因组为127兆碱基对,比其他已测序的球虫基因组大小的两倍还多。比较分析确定了球虫纲中侵袭机制的保守性。然而,肉孢子虫属神经元种缺乏许多负责改变弓形虫属和新孢子虫属宿主效应途径的致密颗粒和棒状体激酶基因。此外,肉孢子虫属神经元种的SRS蛋白种类有所不同,此前认为这些蛋白与弓形虫属的组织包囊形成有关。基于系统的分析确定了一系列代谢创新,包括利用替代能源的能力。最后,我们提出了一个肉孢子虫属神经元种模型,详细说明了促进从纯粹的肠道生活方式(艾美耳属)向能够感染多种中间宿主的异宿主寄生虫转变的保守分子创新。

重要性

肉孢子虫属神经元种是球虫纲的成员,球虫纲是一类单细胞顶复门寄生虫,在全球范围内造成重大经济和医疗负担。肉孢子虫属是疟原虫属、隐孢子虫属、泰勒虫属和艾美耳属的近亲,是最成功的寄生虫属之一;它能够感染所有脊椎动物(鱼类, 爬行动物, 鸟类和哺乳动物,包括人类)。在过去十年中,与急性肉孢子虫病相关的具有临床意义的人类疫情不断增加。在肉孢子虫属物种中,肉孢子虫属神经元种具有广泛的宿主范围,可导致马、海洋哺乳动物和其他几种哺乳动物的致命性脑炎。为了深入了解从纯粹的肠道寄生虫(如艾美耳属)向形成组织包囊的寄生虫(如弓形虫属)的转变,我们展示了肉孢子虫属神经元种的首个基因组序列。与其他球虫基因组的比较突出了驱动其独特生命周期策略的分子创新。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/ee908004e6a5/mbo0041421360006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/d516ec7611c0/mbo0041421360001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/7424d716c974/mbo0041421360005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/ee908004e6a5/mbo0041421360006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/d516ec7611c0/mbo0041421360001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/45f945338bdf/mbo0041421360002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/9dff444e6d34/mbo0041421360003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2929/4337577/4181050188ef/mbo0041421360004.jpg
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